Department of Hematology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, People's Republic of China.
Department of Clinical Medicine, Capital Medical University, Beijing, People's Republic of China.
Stem Cells Transl Med. 2022 Nov 18;11(11):1113-1122. doi: 10.1093/stcltm/szac066.
Post-remission strategies for patients with acute lymphoblastic leukemia (ALL) are limited to the multiagent chemotherapy and allogeneic stem cell transplant (allo-SCT), and cellular therapies are seldom involved. Although chemotherapy combined with mismatched granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell infusion (microtransplant, MST) has been studied in patients with acute myeloid leukemia, its efficacy in ALL is still undetermined. We enrolled 48 patients receiving hyper-CVAD-based MST between July 1, 2009, and January 31, 2018. No acute or chronic graft-versus-host disease occurred in patients receiving MST. Four-year overall survival (OS) and leukemia-free survival (LFS) were 62% and 35%, respectively, and the 4-year relapse rate was 65%. No patient experienced non-relapse mortality. Subgroup analysis showed that OS rates were comparable between groups with different age, risk stratification, minimal residual disease status prior to MST and immunophenotype. Adult patients tended to achieve better 4-year LFS (62% vs. 26%, P = .058) and lower hematologic relapse rate (38% vs. 74%, P = .058) compared with adolescent and young adult patients. Donor chimerism/microchimerism was detectable ranging from 0.002% to 42.78% in 78% (42/54) available samples within 14 days after each infusion and at 3 months or one year after the last cell infusion. Multivariate analyses demonstrated that white blood cells <30 × 109/L at diagnosis and sufficient hyper-CVAD cycles were prognostic factors for better 4-year OS and LFS, while the B-cell phenotype and higher number of infused CD34+ cells in the first cycle were predictors for favorable 4-year LFS. The hyper-CVAD-based MST was a feasible strategy for treating ALL patients with mild toxicity.
基于 Hyper-CVAD 的微小移植治疗急性淋巴细胞白血病患者：一项单中心回顾性研究
急性淋巴细胞白血病（ALL）缓解后的治疗策略仅限于联合化疗和异基因造血干细胞移植（allo-SCT），很少涉及细胞治疗。虽然在急性髓系白血病患者中已经研究了化疗联合非匹配粒细胞集落刺激因子动员外周血单个核细胞输注（微移植，MST），但其在 ALL 中的疗效仍不确定。我们招募了 48 例于 2009 年 7 月 1 日至 2018 年 1 月 31 日期间接受基于 Hyper-CVAD 的 MST 的患者。接受 MST 的患者均未发生急性或慢性移植物抗宿主病。4 年总生存率（OS）和无白血病生存率（LFS）分别为 62%和 35%，4 年复发率为 65%。无患者发生非复发相关死亡。亚组分析显示，不同年龄、风险分层、MST 前微小残留病状态和免疫表型的患者之间 OS 率相当。与青少年和年轻成年患者相比，成年患者 4 年 LFS 更高（62% vs. 26%，P=0.058），血液学复发率更低（38% vs. 74%，P=0.058）。在 78%（42/54）可获得的样本中，在每次输注后 14 天内和最后一次细胞输注后 3 个月或 1 年内，均可检测到供体嵌合率/微嵌合率在 0.002%至 42.78%之间。多变量分析表明，诊断时白细胞<30×109/L 和足够的 Hyper-CVAD 周期是 4 年 OS 和 LFS 更好的预后因素，而 B 细胞表型和第一个周期输注的 CD34+细胞数量较多是 4 年 LFS 良好的预测因素。基于 Hyper-CVAD 的 MST 是一种治疗 ALL 患者的可行策略，具有轻度毒性。
